Stearoyl-coenzyme A Desaturase Research Articles

Betulinic acid induces apoptosis of gallbladder cancer cells via repressing SCD1.

Gallbladder cancer (GBC) is the most common and aggressive malignancy of the biliary tract. Betulinic acid (BetA) has been reported to have anti-inflammatory and antitumor effects; however, the effect of BetA on GBC is still unknown. In this study, we investigated the effect of BetA on five GBC cell lines and found that BetA significantly inhibited the proliferation of NOZ cells but had little inhibitory effect on other GBC cells. BetA disturbed mitochondrial membrane potential and induced apoptosis in NOZ cells. Real-time polymerase chain reaction analysis revealed that stearoyl-coenzyme A desaturase 1 (SCD1) was highly expressed in NOZ cells but low expressed in other GBC cells. BetA inhibited SCD1 expression in a concentration-dependent manner in NOZ cells. Downregulation of SCD1 expression by RNA interference inhibited the proliferation of NOZ cells and induced cell apoptosis. Moreover, BetA inhibited the growth of xenografted tumors and suppressed SCD1 expression in nude mice. Thus, our results showed that BetA induced apoptosis through repressing SCD1 expression in GBC, suggesting that BetA might be an effective agent for the treatment of patients with GBC that highly expresses SCD1.

Sex and Depot Differences in Palmitoleic Acid Content of Human Blood and Fat.

Palmitoleic acid has been classified as an insulin-sensitizing lipokine, but evidence for this from human studies has been inconsistent. We hypothesized that this is related to either the types of samples or conditions under which samples are collected. We measured plasma palmitoleic acid and total free fatty acids (FFA) using ultra-performance liquid chromatography in blood samples collected from 34 adults under a variety of conditions. We collected duplicate samples of adipose (n = 10), FFA (n = 9), and very low density lipoprotein triacylglycerol (VLDL-TAG) (n = 7) to measure the palmitoleic acid as a percentage of total fatty acids. We tested whether the percentage of palmitoleic acid was correlated with insulin resistance, as measured by homeostatic model of insulin resistance (HOMA-IR). Adipose stearoyl-coenzyme A desaturase 1 (SCD-1) protein was measured by capillary Western blotting. FFA-palmitoleic acid percentage increased as a function of total FFA and was greater (p < 0.005) in females than males. Adipose palmitoleic acid percentage was greater in females than males (p < 0.001), as was adipose SCD-1. Palmitoleic acid was greater in femoral fat than in abdominal fat in both females and males (p < 0.001), and correlated positively with HOMA-IR only in females. The test-retest reliability values for percentage palmitoleic acid were 7 ± 10% for adipose, 24 ± 26% for VLDL, and 53 ± 31% for FFA. Because FFA-palmitoleic acid percentage varies as a function of total FFA, investigators should re-evaluate how palmitoleic acid data is presented. The positive relationship between adipose palmitoleic acid and HOMA-IR in females suggests that it is not a potent insulin-sensitizing lipokine in humans.

Endogenous synthesis of milk cis-9,trans-11 conjugated linoleic acid in dairy ewes: Quantification using 13C-labeled vaccenic acid and comparison with estimates based on cobalt administration

Isotopic tracers are used to directly quantify the effect of mammary Δ9-desaturation on milk fatty acid (FA) composition, but very few studies have applied this method to measuring the endogenous synthesis of rumenic acid (RA; cis-9,trans-11 conjugated linoleic acid) in cows and goats, and no publications exist in ewes. In sheep, knowledge about the contribution of stearoyl-coenzyme A desaturase (SCD) to milk FA secretion is derived mostly from indirect estimates based on inhibition of the enzyme by oral administration of cobalt, a cost-effective method that has not been validated to date. To fill both gaps, we conducted an isotopic tracer assay in sheep to quantify the proportion of endogenous RA in milk for the first time in this species. We then compared the results with estimates derived from a Co administration assay performed on the same animals. First, 5 lactating ewes received an intravenous injection of 200 mg of [1-13C]trans-11 18:1 (vaccenic acid, VA), the precursor for RA production by SCD activity. At -24, -15, 0, 9, 24, 33, 48, 57, 72, 81, and 96 h post-injection, we recorded milk yield and collected milk samples to examine fat concentration and FA profile. We conducted compound-specific isotope analysis of VA and RA by gas chromatography-combustion isotope ratio mass spectrometry. Afterward, in the Co administration assay, ewes received a daily dose of 7 mg of Co/kg of body weight for 5 d. We analyzed milk samples for composition before and on the last days of cobalt dosing. On average, 17% of the injected amount of [1-13C]VA was transferred to milk within 96 h post-injection, and up to 29% of the VA taken up by the mammary gland was desaturated to milk RA. Under our conditions, the mean proportion of this conjugated linoleic acid isomer deriving from Δ9-desaturation represented 82 to 90% of the amount secreted in milk. However, the proportion estimated in the Co assay with calculations based on individual FA concentrations was lower (on average, 46%). When we calculated the same estimates based on changes in Δ9-desaturation ratios after Co dosing, the higher values of endogenous RA (75%) did not differ from the results of the isotopic tracer assay. Nevertheless, correlation analysis between the results obtained through [1-13C]VA or Co administration revealed no significant relationship, which would prevent acceptance of the latter as a reliable alternative to isotopic labeling to examine mammary Δ9-desaturation in dairy ewes.

Novel Lipid Long Intervening Noncoding RNA, Oligodendrocyte Maturation-Associated Long Intergenic Noncoding RNA, Regulates the Liver Steatosis Gene Stearoyl-Coenzyme A Desaturase As an Enhancer RNA.

The global obesity epidemic is driving the concomitant rise in nonalcoholic fatty liver disease (NAFLD). To identify new genes involved in central liver functions, we examined liver RNA‐sequence data from 259 patients who underwent morbidly obese bariatric surgery. Of these patients, 84 had normal liver histology, 40 simple steatosis, 43 nonalcoholic steatohepatitis, and the remaining 92 patients had varying degrees of NAFLD based on liver histology. We discovered oligodendrocyte maturation‐associated long intergenic noncoding RNA (OLMALINC), a long intervening noncoding RNA (lincRNA) in a human liver co‐expression network (n = 75 genes) that was strongly associated with statin use and serum triglycerides (TGs). OLMALINC liver expression was highly correlated with the expression of known cholesterol biosynthesis genes and stearoyl‐coenzyme A desaturase (SCD). SCD is the rate‐limiting enzyme in monounsaturated fatty acids and a key TG gene that is known to be up‐regulated in liver steatosis and NAFLD and resides adjacent to OLMALINC on the human chromosome 10q24.31. Next, we functionally demonstrated that OLMALINC regulates SCD as an enhancer‐RNA (eRNA), thus describing the first lincRNA that functions as an eRNA to regulate lipid metabolism. Specifically, we show that OLMALINC promotes liver expression of SCD in cis through regional chromosomal DNA–DNA looping interactions. Conclusion: The primate‐specific lincRNA OLMALINC is a novel epigenetic regulator of the key TG and NAFLD gene SCD.

Deep Lipidomics and Molecular Imaging of Unsaturated Lipid Isomers: A Universal Strategy Initiated by mCPBA Epoxidation.

Cellular lipidome is highly regulated through lipogenesis, rendering diverse double-bond positional isomers (C═C isomer) of a given unsaturated lipid species. In recent years, there are increasing reports indicating the physiological roles of C═C isomer compositions associated with diseases, while the biochemistry has not been broadly investigated due to the challenge in characterizing lipid isomers inherent to conventional mass spectrometry-based lipidomics. To address this challenge, we reported a universal, user-friendly, derivatization-based strategy, MELDI (mCPBA Epoxidation for Lipid Double-bond Identification), which enables both large-scale identification and spatial mapping of biological C═C isomers using commercial mass spectrometers without any instrument modification. With the developed liquid-chromatography mass spectrometry (LC-MS) lipidomics workflow, we elucidated more than 100 isomers among monounsaturated and polyunsaturated fatty acids and glycerophospholipids in human serum, where uncommon isomers of low abundance were quantified for the first time. The capability of MELDI-LC-MS in lipidome analysis was further demonstrated using the differentiated 3T3-L1 adipocytes, providing an insight into the cellular lipid reprogramming upon stearoyl-coenzyme A desaturase 1 (SCD1) inhibition. Finally, we highlighted the versatility of MELDI coupled with ambient mass spectrometry imaging to spatially resolve cancer-associated alteration of lipid isomers in a metastatic mouse tissue section. Our results suggested that MELDI will contribute to current lipidomics pipelines with a deeper level of structural information, allowing us to investigate the underlying lipid biochemistry.

Genetic Polymorphism of SCD1 Gene of Holstein-Friesian Cows in Indonesia

&lt;p class="abstrak2"&gt;Stearoyl-Coenzyme A desaturase 1 (SCD1) belongs to the fatty acid family of desaturases. In lactating ruminants, the SCD1 protein is highly expressed in the mammary gland and is relevant for the fatty acid composition of milk and dairy products. Polymorphism of SCD1 gene in Holstein-Friesian (HF) cows could be used as a basis of molecular selection of cattle in order to increase their productivity. The aim of this study was to investigate the polymorphism of SCD1 gene of Holstein-Friesian cows in Indonesia. A total of 162 blood samples of HF cows were collected from four different locations i.e. Bogor, Sukabumi, Tasikmalaya and Enrekang districts. Genotyping of SCD1 gene used PCR-RFLP method with NcoI restriction enzyme. The result showed that three genotypes (AA, AV and VV) and two alleles (A and V) have successfully found and polymorphic. A allele was dominant in all populations (0.63) and in Hardy Weinberg Equilibrium. The highest A allele was found in Sukabumi (0.78) and the lowest was in Bogor (0.55). Heterozigosity observed and expected reached 0.471 and 0.470, respectively. In conclusion, genetic polymorphism was found in all population with dominant of A allele. This finding can be used as a early genetic information of Holstein-Friesian cattle in Indonesia and to build breeding strategy for improving of productivity especially improving of healthy fat milk. &lt;/p&gt;&lt;p class="abstrak2"&gt;&lt;span&gt;&lt;br /&gt;&lt;/span&gt;&lt;/p&gt;

Sorafenib kills liver cancer cells by disrupting SCD1-mediated synthesis of monounsaturated fatty acids via the ATP-AMPK-mTOR-SREBP1 signaling pathway.

Sorafenib is a multikinase inhibitor that is effective in treating advanced liver cancer. Although its mechanism of action through several established cancer-related protein kinase targets is well-characterized, sorafenib induces variable responses among human tumors, and the cause for this variation is yet unknown. To investigate the underlying mechanisms, we applied mass spectrometry-based proteomic analysis to Huh7.5 human liver cancer cells and found that sorafenib significantly affected the expression of the key lipogenic enzymes, especially stearoyl coenzyme A desaturase 1 (SCD1), in these cells. Given that SCD1 catalyzes the most crucial and rate-limiting step in the synthesis of monounsaturated fatty acids (FAs), we performed a lipidomic analysis, which showed a dramatically altered lipid profile in sorafenib-treated cells. Detection and analysis of free FAs showed that the levels of monounsaturated FAs, including oleate, were significantly decreased in those cells treated by sorafenib. Addition of oleate protected liver cancer cells from sorafenib-induced death and alleviated the abnormalities of mitochondrial morphology and function caused by the drug. Treatment with sorafenib suppressed ATP production, resulting in AMPK activation via phosphorylation. Further secondary effects included reduction of the levels of sterol regulatory element-binding protein 1 (SREBP1) and the phosphorylation of mammalian target of rapamycin (mTOR) in liver cancer cells. These effects were partly abolished in the presence of compound C (an AMPK inhibitor) and ATP and adenosine, and SREBP1c overexpression also could be resistant to the effects of sorafenib, suggesting that the sorafenib-induced reduction in cell viability was mediated by the ATP-AMPK-mTOR-SREBP1 signaling pathway. Taken together, our results suggest that sorafenib's anticancer activity in liver cancer cells is based on the inhibition of ATP production, SCD1 expression, and monounsaturated FA synthesis. In addition, the decreased monounsaturated FA synthesis further triggered the more serious reduction of ATP production in sorafenib-treated cells. To our knowledge, this is the first evidence that sorafenib disrupts lipogenesis and triggers liver cancer cell death by targeting SCD1 through the ATP-AMPK-mTOR-SREBP1 pathway.-Liu, G., Kuang, S., Cao, R., Wang, J., Peng, Q., Sun, C. Sorafenib kills liver cancer cells by disrupting SCD1-mediated synthesis of monounsaturated fatty acids via the ATP-AMPK-mTOR- SREBP1 signaling pathway.

Expression of Stearoyl Co-enzyme A desaturase (SCD) gene during the juvenile age in layer chicken

Stearoyl-CoA desaturase (SCD) is key enzyme in the production of triglycerides and cholesterol. Present study was conducted to know the expression pattern of the Stearoyl-CoA desaturase (SCD) gene in liver during juvenile age (0 day, 14th day, 28th day and 42nd day) in layer birds. Expression of SCD gene increased from the day of hatch to 42nd day, as the body weight and fat deposition increased. The mRNA expression levels of SCD gene during day 0 was differed significantly (P less than 0.05) with expression levels during other juvenile ages. When compared with SCD expression levels on the day 0 expression levels were up-regulated by 8198.64, 7245.99 and 5587.77 folds over day 14, 28 and 42 respectively. Serum concentration of triglycerides and cholesterol were found to be proportional to the expression levels of SCD gene in liver. It is concluded that SCD expression varied among different age groups during juvenile stages and had significant association with serum triglycerides and cholesterol concentration in layer chicken.

Stearoyl-coenzyme A desaturase 1 is required for lipid droplet formation in pig embryo.

Lipid droplets (LD) provide a source of energy, and their importance during embryogenesis has been increasingly recognized. In particular, pig embryos have larger amounts of intercellular lipid bilayers than other mammalian species, suggesting that porcine embryos are more dependent on lipid metabolic pathways. The objective of the present study was to detect the effect of stearoyl-coenzyme A desaturase 1 (SCD1) on LD formation and to associate these effects with the mRNA abundance of LD formation-related genes (SREBP, ARF1, COPG2, PLD1 and ERK2) in in vitro-produced porcine embryos. To determine the effect of SCD1 on LD formation and related genes, we examined the effects of SCD1 inhibition using CAY10566 (an SCD1 inhibitor, 50 μM) on parthenogenetic embryos. SCD1 inhibition downregulated the mRNA levels of LD formation-related genes and embryo development. Our results revealed that SCD1 functions in the regulation of LD formation via phospholipid formation and embryo development. In addition, we treated parthenogenetic embryos with oleic acid (100 μM), which led to a significant increase in the blastocyst formation rate, LD size and number compared to controls. Remarkably, the adverse effects of the SCD1 inhibitor could be counteracted by oleic acid. These data suggest that porcine embryos can use exogenous oleic acid as a metabolic energy source.

Association of the PNPLA2, SCD1 and Leptin Expression with Fat Distribution in Liver and Adipose Tissue From Obese Subjects

The expansion of adipose tissue is regulated by insulin and leptin through sterol regulatory element-binding protein-1c (SREBP-1c), up-regulating lipogenesis in tissues by Stearoylcoenzyme A desaturase 1 (SCD1) enzyme, while adipose triglyceride lipase (ATGL) enzyme is key in lipolysis. The research objective was to evaluate the expression of Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1), SCD1, Patatin Like Phospholipase Domain Containing 2 (PNPLA2), and leptin (LEP) genes in hepatic-adipose tissue, and related them with the increment and distribution of fat depots of individuals without insulin resistance. Thirty-eight subjects undergoing elective cholecystectomy with liver and adipose tissue biopsies (subcutaneous-omental) are included. Tissue gene expression was assessed by qPCR and biochemical parameters determined. Individuals are classified according to the body mass index, classified as lean (control group, n=12), overweight (n=11) and obesity (n=15). Abdominal adiposity was determined by anthropometric and histopathological study of the liver. Increased SCD1 expression in omental adipose tissue (p=0.005) and PNPLA2 in liver (p=0.01) were found in the obesity group. PNPLA2 decreased expression in subcutaneous adipose tissue was significant in individuals with abdominal adiposity (p=0.017). Anthropometric parameters positively correlated with liver PNPLA2 and the expression of liver PNPLA2 with serum leptin. SCD1 increased levels may represent lipid storage activity in omental adipose tissue. Liver PNPLA2 increased expression could function as a primary compensatory event of visceral fat deposits associated to the leptin hormone related to the increase of adipose tissue.

The Role of Stearoyl-coenzyme A Desaturase 1 in Liver Development, Function, and Pathogenesis

Stearoyl-coenzyme A desaturase 1 (SCD1) is a microsomal enzyme that controls fatty acid metabolism and is highly expressed in hepatocytes. SCD1 may play a key role in liver development and hepatic lipid homeostasis through promoting monounsaturated protein acylation and converting lipotoxic saturated fatty acids into monounsaturated fatty acids. Imbalanced activity of SCD1 has been implicated in fatty liver induction, inflammation and stress. In this review, the role of SCD1 in hepatic development, function and pathogenesis is discussed. Additionally, emerging novel therapeutic agents targeting SCD1 for the treatment of liver disorders are presented.

Lipidomics reveal aryl hydrocarbon receptor (Ahr)-regulated lipid metabolic pathway in alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis

1. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry (UPLC-ESI-QTOF MS)-based lipidomics was employed to elucidate new mechanism of alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis in mice.2. Multiple lipid components significantly increased in ANIT-induced intrahepatic cholestasis, including PC 16:0, 20:4, PC 16:0, 22:6, PC 16:0, 18:2, LPC 18:2, PC 18:2, LPC 18:1, PC 18:1, 14:0, SM 18:1, 16:0, oleoylcarnitine and palmitoylcarnitine. This alteration of lipid profile was induced by the changed expression of genes choline kinase (Chk) a, sphingomyelin phosphodiesterase (SMPD) and stearoyl-coenzyme A desaturase 1 (SCD1).3. Knockout of aryl hydrocarbon receptor (Ahr) in mice can significantly reverse ANIT-induced intrahepatic cholestasis, as indicated by lowered ALT, AST and ALP activity, and liver histology. Aryl hydrocarbon receptor knockout significantly reversed ANIT-induced lipid metabolism alteration through regulating the expression of Chka.4. In conclusion, this study demonstrated ANIT-induced lipid metabolism disruption might be the potential pathogenesis of ANIT-induced intrahepatic cholestasis in mice.

Protection by the Total Flavonoids from Rosa laevigata Michx Fruit against Lipopolysaccharide-Induced Liver Injury in Mice via Modulation of FXR Signaling.

We previously reported the effects of the total flavonoids (TFs) from Rosa laevigata Michx fruit against carbon tetrachloride-induced liver damage, non-alcoholic fatty liver disease, and liver ischemia-reperfusion injury. However, there have been no papers reporting the role of R. laevigata TFs against lipopolysaccharide (LPS)-induced liver injury. In this paper, liver injury in mice was induced by LPS, and R. Laevigata extract was intragastrically administered to the mice for 7 days. Biochemical parameters in serum and liver tissue were examined, and pathological changes were observed by transmission electron microscopy, hematoxylin and eosin (H&E) and Oil Red O staining. The results showed that the TFs markedly reduced serum ALT (alanine transferase), AST (aspartate transaminase), TG (total triglyceride), and TC (total cholesterol) levels and relative liver weights and improved liver pathological changes. In addition, the TFs markedly decreased tissue MDA (malondialdehyde) level and increased the levels of SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase). A mechanistic study showed that the TFs significantly increased the expression levels of Nrf2 (nuclear erythroid factor2-related factor 2), HO-1 (heme oxygenase-1), NQO1 (NAD(P)H dehydrogenase (quinone 1), GCLC (glutamate-cysteine ligase catalytic subunit), and GCLM (glutamate-cysteine ligase regulatory subunit) and decreased Keap1 (Kelch-like ECH-associated protein 1) level by activating FXR (farnesoid X receptor) against oxidative stress. Furthermore, the TFs markedly suppressed the nuclear translocation of NF-κB (nuclear factor-kappa B) and subsequently decreased the expression levels of IL (interleukin)-1β, IL-6, HMGB-1 (high -mobility group box 1), and COX-2 (cyclooxygenase-2) by activating FXR and FOXO3a (forkhead box O3) against inflammation. Besides, the TFs obviously reduced the expression levels of SREBP-1c (sterol regulatory element-binding proteins-1c), ACC1 (acetyl-CoA carboxylase-1), FASN (fatty acid synthase), and SCD1 (stearoyl-coenzyme A desaturase 1), and improved CPT1 (carnitine palmitoyltransferase 1) level by activating FXR to regulate lipid metabolism. Our results suggest that TFs exhibited protective effect against LPS-induced liver injury by altering FXR-mediated oxidative stress, inflammation, and lipid metabolism, and should be developed as an effective food and healthcare product for the therapy of liver injury in the future.

Dietary threonine supplementation improves hepatic lipid metabolism of Pekin ducks

The present study was conducted to evaluate the regulatory role of threonine (Thr) on hepatic lipid metabolism by determining the effects of dietary Thr concentration on lipid deposition and on genes related to lipid expression in the liver of Pekin duck. In total, 240 1-day-old ducklings were randomly allocated according to the average bodyweight to one of five dietary treatments with six replicate cages of eight birds per cage for each treatment. Birds were fed diets with 0.52%, 0.59%, 0.66%, 0.73% and 0.80% Thr (as-fed basis) from 1 to 21 days of age respectively. The results showed that dietary Thr supplementation increased average daily gain (P &amp;lt; 0.0001), average daily feed intake (P &amp;lt; 0.0001) and abdominal fat percentage (P &amp;lt; 0.04), while it decreased feed to gain ratio (P &amp;lt; 0.0001), the hepatic contents of total lipid (P &amp;lt; 0.003) and triglycerides (P &amp;lt; 0.003) of Pekin ducks. However, dietary Thr supplementation had no influence (P &amp;gt; 0.05) on the concentration of hepatic cholesterol, and plasma amino acids and biochemical parameters of Pekin ducks. Moreover, Thr-unsupplemented control diet upregulated (P &amp;lt; 0.05) hepatic gene expression related to lipid uptake (fatty acid-binding protein, apolipoprotein A4, lipoprotein lipase), fatty acid synthesis (sterol regulatory element-binding protein 1c, malic enzyme), fatty acid β-oxidation (peroxisome proliferator-activated receptor α, fatty acyl– coenzyme A (CoA) oxidase), ketogenesis (hydroxymethylglutaryl–CoA synthase 1, and acetyl–CoA synthetase1), responsive genes to amino acid deficiency (general control non-derepressible 2 (GCN2), GCN1, eukaryotic initiation factor 2α, impact RWD domain protein (IMPACT)), and triglyceride transport (apolipoprotein B) of Pekin ducks. In addition, dietary Thr deficiency had no effect on the expression of stearoyl CoA desaturase, fatty acid synthase, and ATP–citrate lyase in the liver of Pekin ducks. It is suggested that dietary Thr supplementation improved hepatic lipid metabolism of Pekin ducks by regulating lipid synthesis, transport and oxidation.

Primary Culture of Human Cumulus Cells Requires Stearoyl-Coenzyme A Desaturase 1 Activity for Steroidogenesis and Enhancing Oocyte In Vitro Maturation

Stearoyl-coenzyme A desaturase 1 (SCD1) is a key enzyme in lipid metabolism and is expressed in cumulus cells. The objective of the present study was to evaluate the effect of SCD1 inhibition in human cumulus cells on triglyceride content, steroidogenesis, and oocyte in vitro maturation. Human cumulus cells were exposed to SCD1 inhibitor CAY10566 (SCDinhib) alone or in combination with oleic acid in primary culture. The SCDinhib markedly suppressed triglyceride accumulation (-47%, P = .01), aromatase gene expression (-36%, P = .02), and estradiol production (-49%, P = .01) even at a dose not affecting cell viability and apoptosis. Human immature oocytes at the germinal vesicle (GV) stage were cocultured with pretreated cumulus cells. The rate of oocytes reaching the metaphase II stage was significantly lower in coculture with SCDinhib-treated cumulus cells than with control cumulus cells (-18%, P < .01), which recovered by oleic acid supplementation. This finding on in vitro maturation rate was also reproducible with mouse GV oocytes. The results suggest that SCD1 activity is required for cumulus cell lipid storage and steroidogenesis. In addition, oocyte maturation is negatively affected by SCD1 inhibition in cumulus cells, possibly due to a deficient lipid-mediated paracrine support.

Human charcoal-stripped serum supplementation enhances both the stearoyl-coenzyme a desaturase 1 activity of cumulus cells and the in vitro maturation of oocytes

Obtaining a better outcome in assisted reproductive technology remains to be attained. In the case of in vitro fertilization (IVF), oocyte maturity is paramount for achieving a successful pregnancy. Maternal serum supplementation of in vitro maturation (IVM) medium can increase the rate of oocyte IVM. The aim of the present study was to compare the effect of whole and charcoal-stripped serum supplementation on IVM and the activity index of stearoyl-coenzyme A desaturase 1 (SCD1) in cumulus cells enclosing the oocyte as a molecular indicator of oocyte quality. Cumulus cells and germinal vesicle immature oocytes were collected from 76 women with polycystic ovarian syndrome during an IVF cycle. Serum samples were pooled from healthy women and were applied as whole or charcoal-stripped serum supplements. SCD1 expression and activity were measured by quantitative polymerase chain reaction (PCR) and gas-liquid chromatography, respectively. Charcoal-stripped serum at an amount of 10% showed a higher potency in increasing the SCD1 expression and activity index than whole serum (>1.5 fold, p < 0.001). An increase in the IVM rate was also observed in oocytes cultured in the presence of 10% charcoal-stripped serum compared to the control group (1.9 fold, p = 0.031). Therefore, charcoal-based lipid depletion as a simple and preparative strategy may increase the beneficial effect of serum supplementation in oocyte IVM culture.

Plasma fatty acids as markers for desaturase and elongase activities in spinal cord injured males

Objective: To investigate the use of surrogate plasma fatty acid analysis to provide further insights into the underlying adiposity and the development of metabolic syndrome in men with spinal cord injury (SCI).Design: Case-control, cross-sectional study.Setting: Community-based individuals with spinal cord injury and healthy controls.Participants: Twenty men with SCI age, height and weight matched with 20 able-bodied controls.Outcome Measures: Lean tissue (LTM) and fat mass (FM) were determined using dual energy X-ray absorptiometry. Fasting blood samples were taken for analysis of fatty acids, adiponectin, insulin, glucose and leptin. Enzymatic indices were calculated using relevant fatty acids.Results: Total FM, leptin, stearoyl coenzyme A desaturase (SCD) Δ9 (SCD-16, 16:1/16:0, and SCD-18, 18:1/18:0) indices and Δ6 desaturase index were significantly higher (P < 0.05) in the SCI group than the controls. Significant differences between the groups was observed for several individual fatty acids. Correlational analysis revealed a different pattern between blood biomarkers and indices of SCDs, de novo lipogenesis and elongase. Associations between the desaturase and elongase indices and biomarkers in the controls followed those reported elsewhere for able bodied participants; the same associations were not observed in the SCI group.Conclusion: We have identified disturbances in fatty acid biosynthesis in SCI individuals likely associated with the development of adipose tissue below the lesion and a decrease in LTM. Loss of LTM may disturb the normal skeletal muscle-fatty acid metabolic processes leading to the disruption of metabolic homeostasis, previously identified in persons with SCI.

SCD1 Confers Temozolomide Resistance to Human Glioma Cells via the Akt/GSK3β/β-Catenin Signaling Axis.

Resistance to temozolomide (TMZ), the standard chemotherapy agent for glioblastoma (GBM), poses a major clinical challenge to GBM prognosis. Understanding the mechanisms of TMZ resistance can help to identify novel drug targets and more effective therapies. Recent studies suggest that bioenergetic alterations of cancer cells play important roles in drug resistance. In our study, the altered metabolism of cancer cells was observed using a metabolic PCR array. We found that stearoyl-coenzyme A desaturase 1 (SCD1), a key rate-limiting enzyme for synthesis of monounsaturated fatty acids, was significantly upregulated in TMZ-resistant GBM cells compared to their parental counterparts. Overexpression of SCD1 promoted resistance to TMZ in parental GBM cells, whereas SCD1 downregulation by siRNA could re-sensitize TMZ-resistant cells in vitro. Combinational treatment of TMZ and an SCD1-specific inhibitor showed a combined inhibitory effect on TMZ-resistant glioma cells. We also observed that overexpression of SCD1 promoted Akt/GSK3β/β-catenin signaling, while silencing of SCD1 inhibited the signaling. The combination of an Akt activator with exogenous SCD1 or the combined inhibition of Akt and enforced expression of SCD1 resulted in the most significant changes of Akt signaling. Functionally, significantly lower viability and mobility rates were observed in TMZ-resistant cells when treated with Akt inhibitors and an SCD1 inhibitor simultaneously compared to when treated individually. In conclusion, our study identified SCD1 along with its functional pathway as a novel target in the development of TMZ resistance. SCD1 inhibition used alone or in combination with Akt inhibition could effectively overcome TMZ resistance in gliomas.

Stearoyl coenzyme A desaturase

Background: Oral cancer is a major public health problem in many parts of South Asia and ranking third among the cancer types in India. Numerous diagnostic, prognostic and metastatic biomarkers have been employed till date to assess various carcinomas. Stearoyl coenzyme A desaturase (SCD) is one such recently introduced biomarker that regulates key cell cycle events in normal cells and during carcinogenesis in neoplastic cells. Although SCD has been used to analyze the prognosis of breast and renal cell carcinomas, its role in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) remains unexplored. Therefore, there is a need to analyze the role of SCD in OED and OSCC to predict their biologic behaviour. Objectives: To assess the expression levels of SCD in OED and OSCC samples and correlate them with normal oral mucosa (NOM) to determine their prognostic potential. Methodology: Fifty five tissue samples of OED (20), OSCC (20) and NOM (15) was subjected to immunohistochemistry using SCD. Clinical details and follow-up data (3 years) were recorded. Clinical and histopathological parameters were statistically analyzed using descriptive statistics, univariate and multivariate analyses, Kruskal–Wallis analysis of variance test and Mann–Whitney U tests. Results: Descriptive analysis on OED and NOM showed a statistically significant difference in age between OED and NOM ( p = 0.002). Univariate analysis of OSCC cases by log-rank test revealed significant results in the usage of smoked and smokeless tobacco and clinical staging of OSCC ( p = 0.044). Significantly increased SCD expression was identified with poor survival rate ( p = 0.028). However, multivariate analysis of OSCC was statistically insignificant ( p = 1.00). A significantly increased SCD expression was observed in OED and OSCC when compared to NOM ( p = 0.001). The expression of SCD was significantly high in OSCC when compared to OED ( p = 0.029). Although an increased expression of SCD was appreciated in higher grades of OED and poorly differentiated squamous cell carcinoma, a statistical significance was not achieved ( p = 0.546 and 0.388, respectively). Conclusion: The expression of SCD in OED was higher than NOM suggesting changes in cell cycle control in OED. An enhanced expression of SCD was identified in OSCC when compared to OED. Correlating the SCD expression with survival rate in OSCC patients revealed an increased SCD expression with diminished survival rate, indicating that SCD may be used to predict prognosis. However, the role of SCD in assessing the prognostic potential within the grades of OED and OSCC requires future research.

Substrate specificity and membrane topologies of the iron-containing ω3 and ω6 desaturases from Mortierella alpina.

Polyunsaturated fatty acids (PUFAs) are essential lipids for cell function, normal growth, and development, serving as key structural components of biological membranes and modulating critical signal transduction events. Omega-3 (n-3) long chain PUFAs (LC-PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to protect against inflammatory diseases and enhance brain development and function. This had led to a marked increase in demand for fish and fish oils in human diets, supplements, and aquaculture and created a need for new, sustainable n-3 LC-PUFA sources. We have studied for the first time homogenous preparations of the membrane-type ω6 and ω3 fatty acid desaturases from the fungus Mortierella alpina, as a model system to produce PUFAs. These desaturases possess a di-iron metal center and are selective for 18:1 n-9 and 18:2 n-6 acyl-CoA substrates, respectively. Sequence alignments and membrane topology predictions support that these enzymes have unique cap regions that may include the rearrangement and repositioning of the active site, especially when compared to the mammalian stearoyl-coenzyme A desaturase-1 (SCD1) and the related sphingolipid α-hydroxylase (Scs7p) that act upon different substrates.